2023年 新着論文 18 細胞情報学分野から論文が発表されました
HNRNPU facilitates antibody class-switch recombination through C-NHEJ promotion and R-loop suppressionCell Rep. 2023 Mar 20;42(3):112284. doi: 10.1016/j.celrep.2023.112284. Online ahead of print.
Free article AbstractB cells generate functionally different classes of antibodies through class-switch recombination (CSR), which requires classical non-homologous end joining (C-NHEJ) to join the DNA breaks at the donor and acceptor switch (S) regions. We show that the RNA-binding protein HNRNPU promotes C-NHEJ-mediated S-S joining through the 53BP1-shieldin DNA-repair complex. Notably, HNRNPU binds to the S region RNA/DNA G-quadruplexes, contributing to regulating R-loop and single-stranded DNA (ssDNA) accumulation. HNRNPU is an intrinsically disordered protein that interacts with both C-NHEJ and R-loop complexes in an RNA-dependent manner. Strikingly, recruitment of HNRNPU and the C-NHEJ factors is highly sensitive to liquid-liquid phase separation inhibitors, suggestive of DNA-repair condensate formation. We propose that HNRNPU facilitates CSR by forming and stabilizing the C-NHEJ ribonucleoprotein complex and preventing excessive R-loop accumulation, which otherwise would cause persistent DNA breaks and aberrant DNA repair, leading to genomic instability. Keywords: C-NHEJ; CP: Immunology; CP: Molecular biology; CSR; G-quadruplex; HNRNPU; R-loop; shieldin. Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved. Conflict of interest statementDeclaration of interests The authors declare no competing interests. Full text links |